US7235561B2 - Compound and a composition including such a compound - Google Patents

Compound and a composition including such a compound Download PDF

Info

Publication number
US7235561B2
US7235561B2 US10/156,759 US15675902A US7235561B2 US 7235561 B2 US7235561 B2 US 7235561B2 US 15675902 A US15675902 A US 15675902A US 7235561 B2 US7235561 B2 US 7235561B2
Authority
US
United States
Prior art keywords
alkyl
cycloalkyl
alkoxy
hydroxy
stands
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related, expires
Application number
US10/156,759
Other languages
English (en)
Other versions
US20040102630A1 (en
Inventor
Thomas Brumby
Rolf Jautelat
Olaf Prien
Martina Schäfer
Gerhard Siemeister
Ulrich Lücking
Christoph Huwe
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Bayer Pharma AG
Original Assignee
Schering AG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from DE10127581A external-priority patent/DE10127581A1/de
Priority claimed from DE10212098A external-priority patent/DE10212098A1/de
Application filed by Schering AG filed Critical Schering AG
Assigned to SCHERING AG reassignment SCHERING AG RESUBMISSION OF ASSIGNMENT, DOCUMENT ID NO. 102279765. THE DATES ARE ACTUALLY AS IDENTIFIED BELOW Assignors: HUWE, CHRISTOPH, SCHAEFER, MARTINA, SIEMEISTER, GERHARD, BRUMBY, THOMAS, JAUTELAT, ROLF, LUECKING, ULRICH, PRIEN, OLAF
Priority to US10/842,419 priority Critical patent/US7291624B2/en
Publication of US20040102630A1 publication Critical patent/US20040102630A1/en
Application granted granted Critical
Priority to US11/819,307 priority patent/US7598260B2/en
Publication of US7235561B2 publication Critical patent/US7235561B2/en
Assigned to BAYER SCHERING PHARMA AKTIENGESELLSCHAFT reassignment BAYER SCHERING PHARMA AKTIENGESELLSCHAFT CHANGE OF NAME (SEE DOCUMENT FOR DETAILS). Assignors: SCHERING AKTIENGESELLSCHAFT
Adjusted expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/32—One oxygen, sulfur or nitrogen atom
    • C07D239/42—One nitrogen atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/14—Drugs for dermatological disorders for baldness or alopecia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10—Antimycotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/20—Antivirals for DNA viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/20—Antivirals for DNA viruses
    • A61P31/22—Antivirals for DNA viruses for herpes viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/48—Two nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
    • C07F9/6509—Six-membered rings
    • C07F9/6512—Six-membered rings having the nitrogen atoms in positions 1 and 3

Definitions

  • This invention relates to pyrimidine derivatives, their production as well as their use as medications for treating various diseases.
  • the CDKs (cyclin-dependent kinase) is an enzyme family that plays an important role in the regulation of the cell cycle and thus is an especially advantageous target for the development of small inhibitory molecules.
  • Selective inhibitors of the CDKs can be used for treating cancer or other diseases that cause disruptions of cell proliferation.
  • Pyrimidines and analogs are already described as active ingredients, such as, for example, the 2-anilino-pyrimidines as fungicides (DE 4029650) or substituted pyrimidine derivatives for treating neurological or neurodegenerative diseases (WO 99/19305).
  • pyrimidine derivatives As CDK-inhibitors, the most varied pyrimidine derivatives are described, for example bis(anilino)-pyrimidine derivatives (WO 00/12486), 2-amino-4-substituted pyrimidines (WO 01/14375), purines (WO 99/02162), 5-cyano-pyrimidines (WO 02/04429), anilinopyrimidines (WO 00/12486) and 2-hydroxy-3-N,N-dimethylaminopropoxy-pyrimidines (WO 00/39101).
  • bis(anilino)-pyrimidine derivatives WO 00/12486
  • 2-amino-4-substituted pyrimidines WO 01/14375
  • purines WO 99/02162
  • 5-cyano-pyrimidines WO 02/04429
  • anilinopyrimidines WO 00/12486
  • the object of this invention is to provide compounds that have better properties than the inhibitors that are already known.
  • the substances that are described here are more effective, since they already inhibit in the nanomolar range and can be distinguished from other already known CDK-inhibitors such as, e.g., olomoucine and roscovitine. It has now been found that compounds of general formula I in which
  • Alkyl is defined in each case as a straight-chain or branched alkyl radical, such as, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, hexyl, heptyl, octyl, nonyl and decyl.
  • alkyl radical such as, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, hexyl, heptyl, octyl, nonyl and decyl.
  • Alkoxy is defined in each case as a straight-chain or branched alkoxy radical, such as, for example, methyloxy, ethyloxy, propyloxy, isopropyloxy, butyloxy, isobutyloxy, sec-butyloxy, tert-butyloxy, pentyloxy, isopentyloxy, or hexyloxy.
  • Alkylthio is defined in each case as a straight-chain or branched alkylthio radical, such as, for example, methylthio, ethylthio, propylthio, isopropylthio, butylthio, isobutylthio, sec-butylthio, tert-butylthio, pentylthio, isopentylthio or hexylthio.
  • Cycloalkyl is defined in general as monocyclic alkyl rings, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl or cyclodecyl, but also bicyclic rings or tricyclic rings such as, for example, norbornyl, adamantanyl, etc.
  • ring systems in which optionally one or more possible double bonds can be contained in the ring, are defined as, for example, cycloalkenyls, such as cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, or cycloheptenyl, whereby the linkage can be carried out both to the double bond and to the single bonds.
  • cycloalkenyls such as cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, or cycloheptenyl
  • a and B, R 3 and R 4 , X and R 2 in each case independently of one another, together form a C 3 -C 10 -cycloalkyl ring, which optionally can be interrupted by one or more heteroatoms, such as nitrogen atoms, oxygen atoms and/or sulfur atoms, and/or can be interrupted by one or more ⁇ C ⁇ O groups in the ring and/or optionally one or more possible double bonds can be contained in the ring, however, the above-mentioned definitions are also intended to include heteroaryl radical or heterocycloalkyl and heterocycloalkenyl.
  • Halogen is defined in each case as fluorine, chlorine, bromine or iodine.
  • alkenyl substituents in each case are straight-chain or branched, whereby, for example, the following radicals are meant: vinyl, propen-1-yl, propen-2-yl, but-1-en-1-yl, but-1-en-2-yl, but-2-en-1-yl, but-2-en-2-yl, 2-methyl-prop-2-en-1-yl, 2-methyl 1-en-1-yl, but-1-en-3-yl, ethinyl, prop-1-in-1-yl, but-1-in-1-yl, but-2-in-1-yl, but-3-en-1-yl, and allyl.
  • Alkinyl is defined in each case as a straight-chain or branched alkinyl radical that contains 2-6, preferably 2-4 C atoms.
  • the following radicals can be mentioned: acetylene, propin-1-yl, propin-3-yl, but-1-in-1-yl, but-1-in-4-yl, but-2-in-1-yl, but-1-in-3-yl, etc.
  • the aryl radical in each case comprises 3-12 carbon atoms and in each case can be benzocondensed.
  • cyclopropenyl cyclopentadienyl
  • phenyl tropyl
  • cyclooctadienyl indenyl
  • naphthyl azulenyl
  • biphenyl fluorenyl, anthracenyl, etc.
  • the heteroaryl radical in each case comprises 3-16 ring atoms, and instead of the carbon can contain one or more heteroatoms that are the same or different, such as oxygen, nitrogen or sulfur, in the ring, and can be monocyclic, bicyclic, or tricyclic and in addition in each case can be benzocondensed.
  • benzo derivatives thereof such as, e.g., quinolyl, isoquinolyl, etc., or azocinyl, indolizinyl, purinyl, etc. and benzo derivatives thereof; or quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, pteridinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, xanthenyl, oxepinyl, etc.
  • Heterocycloalkyl stands for an alkyl ring that comprises 3-12 carbon atoms, which instead of the carbon contains one or more heteroatoms that are the same or different, such as, e.g., oxygen, sulfur or nitrogen.
  • heterocycloalkyls there can be mentioned, e.g.: oxiranyl, oxethanyl, aziridinyl, azetidinyl, tetrahydrofuranyl, pyrrolidinyl, dioxolanyl, imidazolidinyl, pyrazolidinyl, dioxanyl, piperidinyl, morpholinyl, dithianyl, thiomorpholinyl, piperazinyl, trithianyl, quinuclidinyl, etc.
  • Heterocycloalkenyl stands for an alkyl ring that comprises 3-12 carbon atoms, which instead of the carbon contains one or more heteroatoms that are the same or different such as, e.g., oxygen, sulfur or nitrogen, and which is partially saturated.
  • heterocycloalkenyls there can be mentioned, e.g.: pyran, thiin, dihydroacet, etc.
  • the physiologically compatible salts of organic and inorganic bases are suitable as salts, such as, for example, the readily soluble alkali and alkaline-earth salts, as well as N-methyl-glucamine, dimethyl-glucamine, ethyl-glucamine, lysine, 1,6-hexadiamine, ethanolamine, glucosamine, sarcosine, serinol, tris-hydroxy-methyl-amino-methane, aminopropane diol, Sovak base, and 1-amino-2,3,4-butanetriol.
  • the readily soluble alkali and alkaline-earth salts as well as N-methyl-glucamine, dimethyl-glucamine, ethyl-glucamine, lysine, 1,6-hexadiamine, ethanolamine, glucosamine, sarcosine, serinol, tris-hydroxy-methyl-amino-methane, aminopropane diol,
  • physiologically compatible salts of organic and inorganic acids are suitable, such as hydrochloric acid, sulfuric acid, phosphoric acid, citric acid, tartaric acid, i.a.
  • the compounds according to the invention essentially inhibit cyclin-dependent kinases, upon which is based their action, for example, against cancer, such as solid tumors and leukemia; auto-immune diseases such as psoriasis, alopecia, and multiple sclerosis, chemotherapy-induced alopecia and mucositis; cardiovascular diseases such as stenoses, arterioscleroses and restenoses; infectious diseases, such as, e.g., by unicellular parasites, such as trypanosoma, toxoplasma or plasmodium, or produced by fungi; nephrological diseases, such as, e.g., glomerulonephritis, chronic neurodegenerative diseases, such as Huntington's disease, amyotropic lateral sclerosis, Parkinson's disease, AIDS dementia and Alzheimer's disease; acute neurodegenerative diseases, such as ischemias of the brain and neurotraumas; viral infections, such as, e.g., cytomegalic infections,
  • the eukaryotic cell division ensures the duplication of the genome and its distribution to the daughter cells by passing through a coordinated and regulated sequence of events.
  • the cell cycle is divided into four successive phases: the G1 phase represents the time before the DNA replication, in which the cell grows and is sensitive to external stimuli.
  • the S phase the cell replicates its DNA
  • the G2 phase preparations are made for entry into mitosis.
  • mitosis (M phase) the replicated DNA separates, and cell division is completed.
  • CDKs The cyclin-dependent kinases
  • CDKs a family of serine/threonine kinases, whose members require the binding of a cyclin (Cyc) as a regulatory subunit in order for them to activate, drive the cell through the cell cycle.
  • CDK/Cyc pairs are active in the various phases of the cell cycle.
  • CDK/Cyc pairs that are important to the basic function of the cell cycle are, for example, CDK4(6)/CycD, CDK2/CycE, CDK2/CycA, CDK1/CycA and CDK1/CycB.
  • CDK5 Some members of the CDK enzyme family have a regulatory function by influencing the activity of the above-mentioned cell cycle CDKs, while no specific function could be associated with other members of the CDK enzyme family.
  • CDK5 One of the latter, CDK5, is distinguished in that it has an atypical regulatory subunit (p35) that deviates from the cyclins, and its activity is highest in the brain.
  • the entry into the cell cycle and the passage through the “restriction points,” which marks the independence of a cell from further growth signals for the completion of the cell division that has begun, are controlled by the activity of the CDK4(6)/CycD and CDK2/CycE complexes.
  • the essential substrate of these CDK complexes is the retinoblastoma protein (Rb), the product of the retinoblastoma tumor suppressor gene.
  • Rb is a transcriptional co-repressor protein.
  • Rb binds and inactivates transcription factors of the E2F type and forms transcriptional repressor complexes with histone-deacetylases (HDAC) (Zhang, H. S. et al.
  • the phosphorylation of Rb by CDK's is to be treated as equivalent to exceeding the “restriction points.”
  • the activity of the CDK2/CycE and CDK2/CycA complexes is necessary, e.g., the activity of the transcription factors of the E2F type is turned off by means of phosphorylation by CDK2/CycA as soon as the cells are entered into the S-phase.
  • the CDK1 in the complex with CycA or CycB controls the entry into and the passage through phases G2 and M (FIG. 1 ).
  • the passage through the cycle is strictly regulated and controlled.
  • the enzymes that are necessary for the progression through the cycle must be activated at the correct time and are also turned off again as soon as the corresponding phase is passed.
  • Corresponding control points (“checkpoints”) stop the progression through the cell cycle if DNA damage is detected, or the DNA replication or the creation of the spindle device is not yet completed.
  • the activity of the CDKs is controlled directly by various mechanisms, such as synthesis and degradation of cyclins, complexing of the CDKs with the corresponding cyclins, phosphorylation and dephosphorylation of regulatory threonine and tyrosine radicals, and the binding of natural inhibitory proteins. While the amount of protein of the CDKs in a proliferating cell is relatively constant, the amount of the individual cyclins oscillates with the passage through the cycle. Thus, for example, the expression of CycD during the early G1 phase is stimulated by growth factors, and the expression of CycE is induced after the “restriction points” are exceeded by the activation of the transcription factors of the E2F type.
  • Activating and inactivating phosphorylations regulate the activities of the CDKs, for example phosphorylate CDK-activating kinases (CAKs) Thr160/161 of the CDK1, while, by contrast, the families of Wee1/Myt1 inactivate kinases CDK1 by phosphorylation of Thr14 and Tyr15. These inactivating phosphorylations can be destroyed in turn by cdc25 phosphatases.
  • CAKs CDK-activating kinases
  • CDK inhibitor proteins CKIs
  • the protein products of the p21 gene family p21, p27, p57
  • the p16 gene family p15, p16, p18, p19
  • Members of the p21 family bind to cyclin complexes of CDKs 1,2,4,6, but inhibit only the complexes that contain CDK1 or CDK2.
  • Members of the p16 family are specific inhibitors of the CDK4 and CDK6 complexes.
  • control points allow the cell to track the orderly sequence of the individual phases during the cell cycle.
  • the most important control points lie at the transition from G1 to S and from G2 to M.
  • the G1 control point ensures that the cell does not initiate any DNA synthesis unless it has proper nutrition, interacts correctly with other cells or the substrate, and its DNA is intact.
  • the G2/M control point ensures the complete replication of DNA and the creation of the mitotic spindle before the cell enters into mitosis.
  • the G1 control point is activated by the gene product of the p53 tumor suppressor gene.
  • a second branch of the G1 control point comprises the activation of the ATM and Chk1 kinases after DNA damage by UV light or ionizing radiation and finally the phosphorylation and the subsequent proteolytic degradation of the cdc25A phosphatase (Mailand, N. et al. (2000). Rapid Destruction of Human cdc25A in Response to DNA Damage. Science 288, 1425-1429).
  • a shutdown of the cell cycle results from this, since the inhibitory phosphorylation of the CDKs is not removed.
  • the G2/M control point is activated by damage of the DNA, both mechanisms are involved in a similar way in stopping the progression through the cell cycle.
  • the loss of the regulation of the cell cycle and the loss of function of the control points are characteristics of tumor cells.
  • the CDK-Rb signal path is affected by mutations in over 90% of human tumor cells. These mutations, which finally result in inactivating phosphorylation of the RB, include the over-expression of D- and E-cyclins by gene amplification or chromosomal translocations, inactivating mutations or deletions of CDK inhibitors of the p16 type, as well as increased (p27) or reduced (CycD) protein degradation.
  • the second group of genes, which are affected by mutations in tumor cells codes for components of the control points.
  • p53 which is essential for the G1 and G2/M control points, is the most frequently mutated gene in human tumors (about 50%).
  • CDK2/Cyc complexes occupy a decisive position during the cell cycle progression: (1) Both dominant-negative forms of CDK2, such as the transcriptional repression of the CDK2 expression by anti-sense oligonucleotides, produce a stopping of the cell cycle progression. (2) The inactivation of the CycA gene in mice is lethal. (3) The disruption of the function of the CDK2/CycA complex in cells by means of cell-permeable peptides resulted in tumor cell-selective apoptosis (Chen, Y. N. P. et al. (1999). Selective Killing of Transformed Cells by Cyclin/Cyclin-Dependent Kinase 2 Antagonists. Proc. Natl. Acad. Sci USA 96, 4325-4329).
  • the cell cycle is activated by a number of viruses, both by transforming viruses as well as by non-transforming viruses, to make possible the replication of viruses in the host cell.
  • the false entry into the cell cycle of normally post-mitotic cells is associated with various neurodegenerative diseases.
  • the mechanisms of the cell cycle regulation, their changes in diseases and a number of approaches to develop inhibitors of the cell cycle progression and especially the CDKs were already described in a detailed summary in several publications (Sielecki, T. M. et al. (2000). Cyclin-Dependent Kinase Inhibitors: Useful Targets in Cell Cycle Regulation. J. Med. Chem. 43, 1-18; Fry, D. W. & Garrett, M.
  • a pharmaceutical preparation which in addition to the active ingredient for enteral or parenteral administration contains suitable pharmaceutical, organic or inorganic inert carrier materials, such as, for example, water, gelatin, gum arabic, lactose, starch, magnesium stearate, talc, vegetable oils, polyalkylene glycols, etc.
  • suitable pharmaceutical, organic or inorganic inert carrier materials such as, for example, water, gelatin, gum arabic, lactose, starch, magnesium stearate, talc, vegetable oils, polyalkylene glycols, etc.
  • the pharmaceutical preparations can be present in solid form, for example as tablets, coated tablets, suppositories, or capsules, or in liquid form, for example as solutions, suspensions, or emulsions.
  • adjuvants such as preservatives, stabilizers, wetting agents or emulsifiers; salts for changing the osmotic pressure or buffers.
  • injection solutions or suspensions especially aqueous solutions of active compounds in polyhydroxyethoxylated castor oil, are suitable.
  • surface-active adjuvants such as salts of bile acids or animal or plant phospholipids, but also mixtures thereof, as well as liposomes or their components can also be used.
  • tablets, coated tablets or capsules with talc and/or hydrocarbon vehicles or binders such as, for example, lactose, corn or potato starch
  • talc and/or hydrocarbon vehicles or binders such as, for example, lactose, corn or potato starch
  • the administration can also be carried out in liquid form, such as, for example, as a juice, to which optionally a sweetener is added.
  • the dosage of the active ingredients can vary depending on the method of administration, age and weight of the patient, type and severity of the disease to be treated and similar factors.
  • the daily dose is 0.5-1000 mg, preferably 50-200 mg, whereby the dose can be given as a single dose to be administered once or divided into two or more daily doses.
  • Subjects of this invention also include the use of compounds of general formula I for the production of a pharmaceutical agent for treating cancer, auto-immune diseases, cardiovascular diseases, chemotherapy agent-induced alopecia and mucositis, infectious diseases, nephrological diseases, chronic and acute neurodegenerative diseases and viral infections, whereby cancer is defined as solid tumors and leukemia; auto-immune diseases are defined as psoriasis, alopecia and multiple sclerosis; cardiovascular diseases are defined as stenoses, arterioscleroses and restenoses; infectious diseases are defined as diseases that are caused by unicellular parasites; nephrological diseases are defined as glomerulonephritis; chronic neurodegenerative diseases are defined as Huntington's disease, amyotrophic lateral sclerosis, Parkinson's disease, AIDS dementia and Alzheimer's disease; acute neurodegenerative diseases are defined as ischemias of the brain and neurotraumas; and viral infections are defined as cytomegalic infections, herpes, hepatitis B
  • Subjects of this invention also include pharmaceutical agents for treating the above-cited diseases, which contain at least one compound according to general formula I, as well as pharmaceutical agents with suitable formulation substances and vehicles.
  • the compounds of general formula I according to the invention are, i.a., excellent inhibitors of the cyclin-dependent kinases, such as CDK1, CDK2, CDK3, CDK4, CDK5, CDK6, CDK7, CDK8 and CDK9, as well as the glycogen-synthase-kinase (GSK-3 ⁇ ).
  • CDK1, CDK2, CDK3, CDK4, CDK5, CDK6, CDK7, CDK8 and CDK9 as well as the glycogen-synthase-kinase (GSK-3 ⁇ ).
  • the isomer mixtures can be separated into the enantiomers or E/Z isomers according to commonly used methods, such as, for example, crystallization, chromatography or salt formation.
  • the production of the salts is carried out in the usual way by a solution of the compound of formula I being mixed with the equivalent amount of or excess base or acid, which optionally is in solution, and the precipitate being separated or the solution being worked up in the usual way.
  • Substance 40 is produced analogously to Example 2.
  • 0.2 ml of a 0.5 M 4-phenylpiperazine solution in DMPU is added to a solution of 19 mg (0.05 mmol) of substance 51 in N,N′-dimethylpropylurea (DMPU).
  • the reaction mixture is kept for 18 hours at a temperature of 80° C.
  • 3.5 ml of tertiary butyl methyl ether is added, and the organic phase is extracted 5 times with 1.5 ml of H 2 O and then evaporated in a vacuum.
  • the remaining residue is chromatographed on 1.7 g (15 ⁇ M) of Lichrosphere Si60 (gradient: dichloromethane/hexane 1:1 to DCM and then dichloromethane/methanol 99:1 to 93:7).
  • a product yield of 17 mg (64%) is achieved.
  • Example No. 122 202 mg (0.60 mmol) of the compound of Example No. 122 is mixed with 1 ml of water and 0.2 g (1.2 mmol) of bromine and stirred at room temperature. After 24 hours, 0.2 g (1.2 mmol) of bromine is added again, and it is stirred for another 24 hours at room temperature. The solvent is evaporated by means of underpressure, and the remaining residue is purified by chromatography (Flashmaster II, DCM/MeOH 7:3). 17 mg (0.04 mmol,7%) of the product is obtained as a white solid.
  • Example No. 288 289 Yield 52% 70% Mass EI: ESI: M + 465 (5%) MH + 446 358 (40%) (100%) 207 (31%) 444 (93%) 117 (20%)
  • Example No. 291 292 293 Yield 34% 36% 40% Mass ESI: ESI: ESI: MH+ 443 (95%) MH+ 485 (92%) MH + 487 (91%) 445 (99%) 487 (99%) 489 (89%) 373 (32%) 373 (32%)
  • 0.2 mmol of sulfonic acid fluoride is introduced into the reactor of a synthesizer.
  • 1.0 ml of solvent, preferably 2-butanol is added.
  • 0.2 ml (0.2 mmol) of DMAP—dissolve in a solvent, for example DMSO or 2-butanol—and 0.2 ml (0.2 mmol) of the amine, dissolved in 2-butanol, are added in succession via a pipette.
  • the reaction mixture is then stirred for 20 hours at 80° C.
  • the crude product is pipetted off, and the reactor is rewashed with 1.0 ml of THF.
  • the solution of the crude product is then concentrated by evaporation and purified by HPLC.
  • the production of the pyrimidine-sulfonic acid fluorides is carried out analogously to the production of the sulfonic acid amides.
  • the follwing para compunds are also produced similarly to the above-described examples:
  • racemates A and B in each case are separated by means of chiral HPLC.
  • the 4-(diaminocyclohexyl) derivatives that are described below are synthesized via reductive aminations of the described keto derivative with use of triacetoxy borohydride (Abdel-Magid, Carson, Harris, Maryanoff, Sha, J. Org. Chem. 1996, 61, 3849).
  • the keto derivative is obtained by TPAP oxidation (Griffith, Ley, Aldrichimica Acta 1990, 23, 13) of the corresponding alcohol.
  • Another subject of this invention are also those compunds that fall under industrial property right DE 4029650, whose action is in the fungicide range and which are not described as CDK inhibitors, however, and also their use for treating cancer is not described.
  • the invention thus relates in addition to pharmaceutical agents that comprise a compound of general formula I
  • R 2 , R 3 , R 4 , R 7 and R 8 have the meanings that are indicated in general formula I, as well as isomers, diastereomers, enantiomers and salts thereof.
  • the agents according to the invention can also be used for treating cancer, auto-immune diseases, cardiovascular diseases, chemotherapy agent-induced alopecia and mucositis, infectious diseases, nephrological diseases, chronic and acute neurodegenerative diseases and viral infections, whereby cancer is defined as solid tumors and leukemia; auto-immune diseases are defined as psoriasis, alopecia and multiple sclerosis; cardiovascular diseases are defined as stenoses, arterioscleroses and restenoses; infectious diseases are defined as diseases that are caused by unicellular parasites; nephrological diseases are defined as glomerulonephritis; chronic neurodegenerative diseases are defined as Huntington's disease, amyotrophic lateral sclerosis, Parkinson's disease, AIDS dementia and Alzheimer's disease; acute neurodegenerative diseases are defined as isehemias of the brain and neurotraumas; and viral infections are defined as cytomegalic infections, herpes, hepatitis B or C, and HIV diseases.
  • CDK2- and CycE-GST-fusion proteins purified from baculovirus-infected insect cells (Sf9), are obtained by Dr. Dieter Marmé, Stamm für Tumorbiologie [Clinic for Tumor Biology], Freiburg. Histone IIIS, which is used as a kinase substrate, is purchased by the Sigma Company.
  • CDK2/CycE (50 ng/measuring point) is incubated for 15 minutes at 22° C. in the presence of various concentrations of test substances (0 ⁇ m, as well as within the range of 0.01-100 ⁇ m) in assay buffer [50 mmol of tris/HCl pH 8.0, 10 mmol of MgCl 2 , 0.1 mmol of Na ortho-vanadate, 1.0 mmol of dithiothreitol, 0.5 ⁇ m of adenosine triphosphate (ATP), 10 ⁇ g/measuring point of histone IIIS, 0.2 ⁇ Ci/measuring point of 33 P-gammna ATP, 0.05% NP40, 12.5% dimethyl sulfoxide]. The reaction is stopped by adding EDTA solution (250 mmol, pH 8.0, 14 ⁇ l/measuring point).
  • Cultivated human tumor cells are flattened out at a density of 5000 cells/measuring point in a 96-hole multititer plate in 200 ⁇ l of the corresponding growth medium. After 24 hours, the cells of one plate (zero-point plate) are colored with crystal violet (see below), while the medium of the other plates is replaced by fresh culture medium (200 ⁇ l), to which the test substances are added at various concentrations (0 ⁇ m, as well as in the range of 0.01-30 ⁇ m; the final concentration of the solvent dimethyl sulfoxide is 0.5%). The cells are incubated for 4 days in the presence of test substances.
  • the compounds according to the invention are compared to known reference compounds and structurally-similar known compounds in the enzyme test.
  • the result is cited in the following table:

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Oncology (AREA)
  • Virology (AREA)
  • Neurology (AREA)
  • Communicable Diseases (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Urology & Nephrology (AREA)
  • Biochemistry (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Dermatology (AREA)
  • Psychology (AREA)
  • Cardiology (AREA)
  • Vascular Medicine (AREA)
  • Immunology (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Pain & Pain Management (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • AIDS & HIV (AREA)
  • Hematology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
US10/156,759 2001-05-29 2002-05-29 Compound and a composition including such a compound Expired - Fee Related US7235561B2 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US10/842,419 US7291624B2 (en) 2001-05-29 2004-05-11 CDK-inhibitory pyrimidines, their production and use as pharmaceutical agents
US11/819,307 US7598260B2 (en) 2001-05-29 2007-06-26 CDK-inhibitory pyrimidines, their production and use as pharmaceutical agents

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
DE10127581.1 2001-05-29
DE10127581A DE10127581A1 (de) 2001-05-29 2001-05-29 CDK inhibitorische Pyrimidine, deren Herstellung und Verwendung als Arzneimittel
DE10212098A DE10212098A1 (de) 2002-03-11 2002-03-11 CDK inhibitorische Pyrimidine, deren Herstellung und Verwendung als Arzneimittel
DE10212098.6 2002-03-11

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
US10/842,419 Continuation US7291624B2 (en) 2001-05-29 2004-05-11 CDK-inhibitory pyrimidines, their production and use as pharmaceutical agents

Related Child Applications (3)

Application Number Title Priority Date Filing Date
US10/842,419 Division US7291624B2 (en) 2001-05-29 2004-05-11 CDK-inhibitory pyrimidines, their production and use as pharmaceutical agents
US10/842,419 Continuation US7291624B2 (en) 2001-05-29 2004-05-11 CDK-inhibitory pyrimidines, their production and use as pharmaceutical agents
US11/819,307 Continuation US7598260B2 (en) 2001-05-29 2007-06-26 CDK-inhibitory pyrimidines, their production and use as pharmaceutical agents

Publications (2)

Publication Number Publication Date
US20040102630A1 US20040102630A1 (en) 2004-05-27
US7235561B2 true US7235561B2 (en) 2007-06-26

Family

ID=26009483

Family Applications (3)

Application Number Title Priority Date Filing Date
US10/156,759 Expired - Fee Related US7235561B2 (en) 2001-05-29 2002-05-29 Compound and a composition including such a compound
US10/842,419 Expired - Fee Related US7291624B2 (en) 2001-05-29 2004-05-11 CDK-inhibitory pyrimidines, their production and use as pharmaceutical agents
US11/819,307 Expired - Fee Related US7598260B2 (en) 2001-05-29 2007-06-26 CDK-inhibitory pyrimidines, their production and use as pharmaceutical agents

Family Applications After (2)

Application Number Title Priority Date Filing Date
US10/842,419 Expired - Fee Related US7291624B2 (en) 2001-05-29 2004-05-11 CDK-inhibitory pyrimidines, their production and use as pharmaceutical agents
US11/819,307 Expired - Fee Related US7598260B2 (en) 2001-05-29 2007-06-26 CDK-inhibitory pyrimidines, their production and use as pharmaceutical agents

Country Status (23)

Country Link
US (3) US7235561B2 (no)
EP (1) EP1392662B1 (no)
JP (1) JP4291135B2 (no)
KR (1) KR100874791B1 (no)
CN (1) CN100480242C (no)
AR (1) AR036035A1 (no)
AT (1) ATE420077T1 (no)
AU (1) AU2002312933B2 (no)
BR (1) BR0209774A (no)
CA (1) CA2449118A1 (no)
CO (1) CO5540316A2 (no)
DE (1) DE50213202D1 (no)
ES (1) ES2320204T3 (no)
HR (1) HRP20031081A2 (no)
IL (1) IL159120A0 (no)
ME (1) MEP13408A (no)
MX (1) MXPA03010810A (no)
NO (1) NO327129B1 (no)
NZ (1) NZ529654A (no)
PL (1) PL367130A1 (no)
RS (1) RS94703A (no)
RU (1) RU2330024C2 (no)
WO (1) WO2002096888A1 (no)

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060234983A1 (en) * 2005-01-19 2006-10-19 Rigel Pharmaceuticals, Inc. Prodrugs of 2,4-pyrimidinediamine compounds and their uses
US20070293521A1 (en) * 2002-02-01 2007-12-20 Rigel Pharmaceuticals, Inc. 2,4-pyrimidinediamine compounds and their uses
US20070299095A1 (en) * 2002-07-29 2007-12-27 Rigel Pharmaceuticals, Inc. Methods of treating or preventing autoimmune diseases with 2,4-pyrimidinediamine compounds
US20080039447A1 (en) * 2001-05-29 2008-02-14 Thomas Brumby CDK-Inhibitory pyrimidines, their production and use as pharmaceutical agents
US20080152712A1 (en) * 2006-09-26 2008-06-26 David Monteith Rapidly disintegrating lyophilized oral formulations of a thrombin receptor antagonist
US20080182840A1 (en) * 2002-12-20 2008-07-31 Pfizer Inc Pyrimidine derivatives for the treatment of abnormal cell growth
US20080221089A1 (en) * 2005-06-08 2008-09-11 Rigel Pharmaceuticals, Inc. Compositions and methods for inhibition of the jak pathway
US20080306099A1 (en) * 2005-06-08 2008-12-11 Rigel Pharmaceuticals, Inc. Compositions and methods for inhibition of the jak pathway
US20090062270A1 (en) * 2004-11-24 2009-03-05 Rigel Pharmaceuticals, Inc. Spiro 2,4 pyrimidinediamine compounds and their uses
US20090304694A1 (en) * 2006-01-27 2009-12-10 Amgen Inc. Ang2 and Vegf Inhibitor Combinations
US20110159019A1 (en) * 2008-09-01 2011-06-30 Akira Tanaka 2,4-diaminopyrimidine compound
US8354420B2 (en) 2010-06-04 2013-01-15 Genentech, Inc. Aminopyrimidine derivatives as LRRK2 inhibitors
US8815882B2 (en) 2010-11-10 2014-08-26 Genentech, Inc. Pyrazole aminopyrimidine derivatives as LRRK2 modulators
US8927547B2 (en) 2010-05-21 2015-01-06 Noviga Research Ab Pyrimidine derivatives
US9006241B2 (en) 2011-03-24 2015-04-14 Noviga Research Ab Pyrimidine derivatives

Families Citing this family (116)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2451128A1 (en) * 2001-06-26 2003-01-09 Bristol-Myers Squibb Company N-heterocyclic inhibitors of tnf-alpha expression
EP1453516A2 (de) 2001-10-17 2004-09-08 Boehringer Ingelheim Pharma GmbH & Co.KG 5-substituierte 4-amino-2-phenylamino-pyrimdinderivate und ihre verwendung als beta-amyloid modulatoren
UY27487A1 (es) 2001-10-17 2003-05-30 Boehringer Ingelheim Pharma Derivados de pirimidina, medicamentos que contienen estos compuestos, su empleo y procedimiento para su preparación
AU2002367172A1 (en) * 2001-12-21 2003-07-15 Bayer Pharmaceuticals Corporation 2,4-diamino-pyrimidine derivative compounds as inhibitors of prolylpeptidase, inducers of apoptosis and cancer treatment agents
GB0205690D0 (en) 2002-03-09 2002-04-24 Astrazeneca Ab Chemical compounds
GB0205693D0 (en) 2002-03-09 2002-04-24 Astrazeneca Ab Chemical compounds
AU2003208479A1 (en) 2002-03-09 2003-09-22 Astrazeneca Ab 4- imidazolyl substuited pyrimidine derivatives with cdk inhibitiory activity
GB0205688D0 (en) * 2002-03-09 2002-04-24 Astrazeneca Ab Chemical compounds
US20050282814A1 (en) * 2002-10-03 2005-12-22 Targegen, Inc. Vasculostatic agents and methods of use thereof
MXPA05005547A (es) * 2002-11-28 2005-07-26 Schering Ag Pirimidinas inhibidoras de chk, pdk y akt, su produccion y uso como agentes farmaceuticos.
US7109337B2 (en) 2002-12-20 2006-09-19 Pfizer Inc Pyrimidine derivatives for the treatment of abnormal cell growth
UA80767C2 (en) * 2002-12-20 2007-10-25 Pfizer Prod Inc Pyrimidine derivatives for the treatment of abnormal cell growth
WO2004067516A1 (en) 2003-01-30 2004-08-12 Boehringer Ingelheim Pharmaceuticals, Inc. 2,4-diaminopyrimidine derivatives useful as inhibitors of pkc-theta
US7157455B2 (en) * 2003-02-10 2007-01-02 Hoffmann-La Roche Inc. 4-Aminopyrimidine-5-one derivatives
GB0311274D0 (en) 2003-05-16 2003-06-18 Astrazeneca Ab Chemical compounds
GB0311276D0 (en) 2003-05-16 2003-06-18 Astrazeneca Ab Chemical compounds
KR101201603B1 (ko) * 2003-07-30 2012-11-14 리겔 파마슈티칼스, 인크. 자가면역 질환의 치료 또는 예방에 사용하기 위한2,4-피리미딘디아민 화합물
EP1663242B1 (en) * 2003-08-07 2011-04-27 Rigel Pharmaceuticals, Inc. 2,4-pyrimidinediamine compounds and uses as anti-proliferative agents
DE10349423A1 (de) * 2003-10-16 2005-06-16 Schering Ag Sulfoximinsubstituierte Parimidine als CDK- und/oder VEGF-Inhibitoren, deren Herstellung und Verwendung als Arzneimittel
US7511137B2 (en) 2003-12-19 2009-03-31 Rigel Pharmaceuticals, Inc. Stereoisomers and stereoisomeric mixtures of 1-(2,4-pyrimidinediamino)-2-cyclopentanecarboxamide synthetic intermediates
TW200528101A (en) 2004-02-03 2005-09-01 Astrazeneca Ab Chemical compounds
CA2567574C (en) * 2004-04-08 2013-01-08 Targegen, Inc. Benzotriazine inhibitors of kinases
WO2005111022A1 (en) 2004-05-14 2005-11-24 Pfizer Products Inc. Pyrimidines derivatives for the treatment of abnormal cell growth
WO2005111024A1 (en) * 2004-05-14 2005-11-24 Pfizer Products Inc. Pyrimidine derivatives for the treatment of abnormal cell growth
MXPA06013165A (es) 2004-05-14 2007-02-13 Pfizer Prod Inc Derivados de pirimidina para el tratamiento de crecimiento de celulas anormal.
EP1763514A2 (en) 2004-05-18 2007-03-21 Rigel Pharmaceuticals, Inc. Cycloalkyl substituted pyrimidinediamine compounds and their uses
US7534780B2 (en) * 2004-05-21 2009-05-19 Bayer Schering Pharma Aktiengesellschaft Estradiol prodrugs
US20050277625A1 (en) * 2004-05-21 2005-12-15 Ralf Wyrwa Estriol and estetrol prodrugs
WO2006014482A1 (en) 2004-07-08 2006-02-09 Boehringer Ingelheim Pharmaceuticals, Inc. Pyrimidine derivatives useful as inhibitors of pkc-theta
NZ553492A (en) 2004-08-25 2010-11-26 Targegen Inc Triazole derivatives and methods of use
EP1794134A1 (de) * 2004-09-29 2007-06-13 Bayer Schering Pharma Aktiengesellschaft Substituierte 2-anilinopyrimidine als zellzyklus -kinase oder rezeptortyrosin-kinase inhibitoren, deren herstellung und verwendung als arzneimittel
KR20070084067A (ko) * 2004-10-13 2007-08-24 와이어쓰 Ｎ-벤젠설포닐 치환 아닐리노-피리미딘 동족체
GB2420559B (en) 2004-11-15 2008-08-06 Rigel Pharmaceuticals Inc Stereoisomerically enriched 3-aminocarbonyl bicycloheptene pyrimidinediamine compounds and their uses
BRPI0517426A (pt) * 2004-12-17 2008-10-07 Astrazeneca Ab composto, processo para preparar o mesmo, composição farmacêutica, uso de um composto, e, métodos para produzir um efeito anti-proliferação celular, para produzir um efeito inibitório de cdk2, e para tratar uma doença em um animal de sangue quente
JP5475235B2 (ja) 2005-01-21 2014-04-16 アステックス・セラピューティクス・リミテッド 医薬化合物
DE102005008310A1 (de) * 2005-02-17 2006-08-24 Schering Ag Verwendung von CDKII Inhibitoren zur Fertilitätskontrolle
US20060247250A1 (en) * 2005-03-16 2006-11-02 Targegen, Inc. Pyrimidine inhibitors of kinases
EP1705177A1 (en) * 2005-03-23 2006-09-27 Schering Aktiengesellschaft N-aryl-sulfoximine-substituted pyrimidines as CDK- and/or VEGF inhibitors, their production and use as pharmaceutical agents
JP2008540436A (ja) * 2005-05-03 2008-11-20 ライジェル ファーマシューティカルズ， インコーポレイテッド Ｊａｋキナーゼインヒビターおよびそれらの使用
EP1893216A4 (en) * 2005-06-08 2012-08-08 Targegen Inc METHOD AND COMPOSITIONS FOR THE TREATMENT OF EYE DISEASES
EP1741709A1 (en) * 2005-06-28 2007-01-10 Sanofi-Aventis Deutschland GmbH Heteroaryl-substituted amides comprising a saturated linker group, and their use as pharmaceuticals
US20070032514A1 (en) * 2005-07-01 2007-02-08 Zahn Stephan K 2,4-diamino-pyrimidines as aurora inhibitors
CA2617170A1 (en) * 2005-07-30 2007-02-08 Astrazeneca Ab Imidazolyl-pyrimidine compounds for use in the treatment of proliferative disorders
WO2007038387A2 (en) * 2005-09-23 2007-04-05 Yale University Compounds and methods for the treatment of viruses and cancer
DE102005048072A1 (de) * 2005-09-24 2007-04-05 Bayer Cropscience Ag Thiazole als Fungizide
UY29826A1 (es) * 2005-09-30 2007-04-30 Astrazeneca Ab Derivados de pirimidina, sales farmaceuticamente aceptables, esteres de los mismos hidrolisables in vivo, procesos de preparacion y aplicaciones
US20070110751A1 (en) * 2005-10-25 2007-05-17 Maclellan Robb Compositions and methods for reducing infarct size
PT1951684T (pt) * 2005-11-01 2016-10-13 Targegen Inc Inibidores de cinases de tipo biaril-meta-pirimidina
US8604042B2 (en) * 2005-11-01 2013-12-10 Targegen, Inc. Bi-aryl meta-pyrimidine inhibitors of kinases
US8133900B2 (en) * 2005-11-01 2012-03-13 Targegen, Inc. Use of bi-aryl meta-pyrimidine inhibitors of kinases
US20070149508A1 (en) * 2005-11-02 2007-06-28 Targegen, Inc. Six membered heteroaromatic inhibitors targeting resistant kinase mutations
US7705009B2 (en) * 2005-11-22 2010-04-27 Hoffman-La Roche Inc. 4-aminopyrimidine-5-thione derivatives
US20070123500A1 (en) * 2005-11-29 2007-05-31 Gerd Mueller Prodrugs of ERbeta-selective substances, processes for their preparation and pharmaceutical compositions comprising these compounds
US20070197488A1 (en) * 2005-11-29 2007-08-23 Olaf Peters Prodrugs of ERbeta-selective substances, process for their production, and pharmaceutical compositions that contain these compounds
US20070135375A1 (en) * 2005-11-30 2007-06-14 Ralf Wyrwa Sulfamoyl sulfonate prodrugs
US20070135399A1 (en) * 2005-11-30 2007-06-14 Ralf Wyrwa Heteroaromatic sulphonamide prodrugs
EP1803723A1 (de) 2006-01-03 2007-07-04 Bayer Schering Pharma Aktiengesellschaft (2,4,9-triaza-1(2,4)-pyrimidina-3(1,3)-benzenacyclononaphan-3^4-yl)-sulfoximid derivate als selektive inhibitoren der aurora kinase zur behandlung von krebs
DE102006001161A1 (de) * 2006-01-06 2007-07-12 Qiagen Gmbh Verfahren zum Nachweis von Cytosin-Methylierungen
US8962643B2 (en) 2006-02-24 2015-02-24 Rigel Pharmaceuticals, Inc. Compositions and methods for inhibition of the JAK pathway
US8623887B2 (en) * 2006-05-15 2014-01-07 Boehringer Ingelheim International Gmbh Compounds
TW200811169A (en) * 2006-05-26 2008-03-01 Astrazeneca Ab Chemical compounds
CA2655315A1 (en) * 2006-06-15 2007-12-21 Boehringer Ingelheim International Gmbh 2-anilino-4-aminoalkyleneaminopyrimidines
WO2007146981A2 (en) * 2006-06-15 2007-12-21 Boehringer Ingelheim International Gmbh 2-anilino-4-(heterocyclic)amino-pyrimidines as inhibitors of protein kinase c-alpha
EP1878726A1 (en) * 2006-07-12 2008-01-16 Bayer Schering Pharma Aktiengesellschaft Substituted sulphoximines as Tie2 inhibitors and salts thereof, pharmaceutical compositions comprising the same, methods of preparing the same and uses of the same
EP2073803B1 (en) 2006-10-12 2018-09-19 Astex Therapeutics Limited Pharmaceutical combinations
US8883790B2 (en) 2006-10-12 2014-11-11 Astex Therapeutics Limited Pharmaceutical combinations
US8148391B2 (en) 2006-10-23 2012-04-03 Cephalon, Inc. Fused bicyclic derivatives of 2,4-diaminopyrimidine as ALK and c-Met inhibitors
EP1939185A1 (de) * 2006-12-20 2008-07-02 Bayer Schering Pharma Aktiengesellschaft Neuartige Hetaryl-Phenylendiamin-Pyrimidine als Proteinkinaseinhibitoren zur Behandlung von Krebs
US20100144706A1 (en) 2006-12-22 2010-06-10 Boehringer Ingelheim International Gmbh Compounds
DE102007010801A1 (de) * 2007-03-02 2008-09-04 Bayer Cropscience Ag Diaminopyrimidine als Fungizide
CN101678215B (zh) 2007-04-18 2014-10-01 辉瑞产品公司 用于治疗异常细胞生长的磺酰胺衍生物
WO2008140421A2 (en) * 2007-05-15 2008-11-20 S*Bio Pte Ltd Heterocycloalkyl substituted pyrimidine derivatives
KR101294731B1 (ko) * 2007-06-04 2013-08-16 삼성디스플레이 주식회사 어레이 기판, 이를 갖는 표시패널 및 이의 제조방법
US20090030005A1 (en) * 2007-07-19 2009-01-29 Amgen Inc. Combinations for the treatment of cancer
WO2009089277A2 (en) * 2008-01-08 2009-07-16 The Trustees Of The University Of Pennsylvania Rel inhibitors and methods of use thereof
US20100056524A1 (en) * 2008-04-02 2010-03-04 Mciver Edward Giles Compound
US8063058B2 (en) 2008-04-16 2011-11-22 Portola Pharmaceuticals, Inc. Inhibitors of syk and JAK protein kinases
US8138339B2 (en) 2008-04-16 2012-03-20 Portola Pharmaceuticals, Inc. Inhibitors of protein kinases
US8258144B2 (en) * 2008-04-22 2012-09-04 Portola Pharmaceuticals, Inc. Inhibitors of protein kinases
TW201020245A (en) * 2008-08-20 2010-06-01 Schering Corp Ethynyl-substituted pyridine and pyrimidine derivatives and their use in treating viral infections
EP2161259A1 (de) 2008-09-03 2010-03-10 Bayer CropScience AG 4-Halogenalkylsubstituierte Diaminopyrimidine als Fungizide
EP2179992A1 (de) 2008-10-21 2010-04-28 Bayer Schering Pharma Aktiengesellschaft Sulfonsubstituierte Anlinopyrimidinderivative als CDK-Inhibitoren, deren Herstellung und Verwendung als Arzneimittel
EP2179991A1 (de) 2008-10-21 2010-04-28 Bayer Schering Pharma Aktiengesellschaft Sulfoximinsubstituierte Anilino-Pyrimidinderivate als CDK-Inhibitoren, deren Herstellung und Verwendung als Arzneimittel
EP2179993A1 (de) 2008-10-21 2010-04-28 Bayer Schering Pharma Aktiengesellschaft Sulfoxidsubstituierte Anilinopyrimidinderivative als CDK-Inhibitoren, deren Herstellung und Verwendung als Arzneimittel
UY32240A (es) 2008-11-14 2010-06-30 Boeringer Ingelheim Kg Nuevas 2,4-diaminopirimidinas, sus sales farmacéuticamente aceptables, composiciones conteniéndolas y aplicaciones.
DE102009001438A1 (de) 2009-03-10 2010-09-16 Bayer Schering Pharma Aktiengesellschaft Carbonylamino-substituierte Anilino-Pyrimidinderivate als Tyk-Inhibitoren, deren Herstellung und Verwendung als Arzneimittel
US20110071158A1 (en) * 2009-03-18 2011-03-24 Boehringer Ingelheim International Gmbh New compounds
DE102009015070A1 (de) 2009-03-30 2010-10-14 Bayer Schering Pharma Aktiengesellschaft Aminocabonylamino-substituierte Anilino-Pyrimidinderivate als Tyk-Inhibitoren, deren Herstellung und Verwendung als Arzneimittel
TW201100441A (en) 2009-06-01 2011-01-01 Osi Pharm Inc Amino pyrimidine anticancer compounds
US8466155B2 (en) * 2009-10-02 2013-06-18 Boehringer Ingelheim International Gmbh Pyrimidines
DE102010014426A1 (de) 2010-04-01 2011-10-06 Bayer Schering Pharma Aktiengesellschaft Verwendung neuer pan-CDK-Inhibitoren zur Behandlung von Tumoren
DE102010014427A1 (de) 2010-04-01 2011-10-06 Bayer Schering Pharma Aktiengesellschaft Kombinationen neuer pan-CDK-Inhibitoren zur Behandlung von Tumoren
EP2621483A1 (en) 2010-09-27 2013-08-07 Exelixis, Inc. Dual inhibitors of met and vegf for the treatment of castration resistant prostate cancer and osteoblastic bone metastases
AU2010363329A1 (en) 2010-11-07 2013-05-09 Targegen, Inc. Compositions and methods for treating myelofibrosis
PL2646448T3 (pl) 2010-11-29 2017-12-29 OSI Pharmaceuticals, LLC Makrocykliczne inhibitory kinazy
BR112014012396B1 (pt) 2011-11-23 2020-08-25 Portola Pharmaceuticals, Inc inibidores de pirazina quinase, composição, método in vitro para inibição de quinase syk ou via de transdução de sinal, uso dos referidos inibidores e kit
US8791130B2 (en) * 2011-11-29 2014-07-29 Genentech, Inc. Aminopyrimidine derivatives as LRRK2 modulators
EA201491732A1 (ru) 2012-03-21 2015-08-31 Байер Интеллектуэль Проперти Гмбх Применение (rs)-s-циклопропил-s-(4-{[4-{[(1r,2r)-2-гидрокси-1-метилпропил]окси}-5-(трифторметил)пиримидин-2-ил]амино}фенил)сульфоксимида для лечения специфических опухолей
US9931400B2 (en) 2012-09-12 2018-04-03 Samsung Electronics Co., Ltd. Method of combination therapy for prevention or treatment of c-Met or angiogenesis factor induced diseases
WO2014106606A1 (en) * 2013-01-05 2014-07-10 F. Hoffmann-La Roche Ag Nove phenyl/pyridine series substitued by hydroxyethylamino for the treatment of cancer
WO2014173815A1 (en) 2013-04-23 2014-10-30 Bayer Pharma Aktiengesellschaft Use of (rs)-s-cyclopropyl-s-(4-{[4-{[(1r, 2r)-2-hydroxy-1-methylpropyl]oxy}-5- (trifluoromethyl)pyrimidin-2-yl]amino}phenyl)sulphoximide for the treatment of specific tumours
SG11201608242XA (en) * 2014-04-04 2016-10-28 Syros Pharmaceuticals Inc Inhibitors of cyclin-dependent kinase 7 (cdk7)
CN107517589A (zh) 2015-01-08 2017-12-26 小利兰·斯坦福大学托管委员会 提供骨、骨髓及软骨的诱导的因子和细胞
CN108721307B (zh) * 2018-03-20 2021-01-15 重庆医科大学 Cdk2激酶抑制剂在制备乙型肝炎治疗药物中的应用
DK3902547T3 (da) 2018-12-28 2023-12-18 Deciphera Pharmaceuticals Llc Csf1r-hæmmere til anvendelse i cancerbehandling
US20220153722A1 (en) 2019-04-04 2022-05-19 Dana-Farber Cancer Institute, Inc. Cdk2/5 degraders and uses thereof
CA3132656A1 (en) 2019-04-30 2020-11-05 Instituto De Medicina Molecular Joao Lobo Antunes Rank pathway inhibitors in combination with cdk inhibitors
CN111138417B (zh) * 2019-12-18 2021-03-23 浙江工业大学 一种三氮唑修饰的5-氟-2,4-嘧啶二胺类化合物及其应用
CN112110863A (zh) * 2020-08-27 2020-12-22 中山大学 一种磺酰氟类化合物、其制备方法以及通过其制备磺酰胺类化合物的方法
CA3202990A1 (en) * 2020-11-27 2022-06-02 Anrui Biomedical Technology (Guangzhou) Co., Ltd. Aminoheteroaryl kinase inhibitors
CN114105887B (zh) * 2021-09-16 2023-12-01 沈阳药科大学 一种氨基嘧啶衍生物及其制备方法和用途
WO2023226920A1 (en) * 2022-05-27 2023-11-30 Anrui Biomedical Technology (Guangzhou) Co.,Ltd. Aminoheteroaryl kinase inhibitors
CN115304550A (zh) * 2022-07-25 2022-11-08 南通大学 哌嗪苯基氨基取代的嘧啶氨基酸衍生物及制备方法与应用
CN115232076A (zh) * 2022-07-25 2022-10-25 南通大学 苯氨基取代的嘧啶氨基酸衍生物及其制备方法与应用
CN115304551A (zh) * 2022-07-25 2022-11-08 南通大学 2-((4-吗啉苯基)氨基)嘧啶氨基酸衍生物及其制备方法与应用
WO2024059010A1 (en) * 2022-09-13 2024-03-21 Genesis Therapeutics, Inc. Compounds for treating cancer

Citations (87)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3947467A (en) 1973-08-02 1976-03-30 Eli Lilly And Company 3-(5-Nitro-2-imidazolyl) pyrazoles
US4012495A (en) 1974-03-20 1977-03-15 Schering Aktiengesellschaft 4-(Polyalkoxyphenyl)-2-pyrrolidones
US4015017A (en) 1974-01-15 1977-03-29 Laboratoires Pharmascience Certain biphenyl derivatives used to treat disorders caused by increased capillary permeability
US4153713A (en) 1975-09-18 1979-05-08 Schering Aktiengesellschaft 4-(Polyalkoxyphenyl)-2-pyrrolidones (II)
US4193926A (en) 1974-03-20 1980-03-18 Schering Aktiengesellschaft 4-(Polyalkoxy phenyl)-2-pyrrolidones
US4303649A (en) 1978-06-15 1981-12-01 Imperial Chemical Industries Limited 1-Phenyl-2-aminoethanol derivatives
US4548940A (en) 1982-12-23 1985-10-22 Smith Kline & French Laboratories Limited Pyridylaminoalkylaminopyrimidones useful as histamine H1 -antagonists
EP0224339A2 (en) 1985-10-30 1987-06-03 Kumiai Chemical Industry Co., Ltd. Pyrimidine derivative, process for preparing same and agricultural or horticultural fungicidal composition containing same
US4694009A (en) 1984-06-25 1987-09-15 Ciba-Geigy Corporation Pesticidal compositions
WO1987006576A1 (en) 1986-04-29 1987-11-05 Pfizer Inc. Calcium independent camp phosphodiesterase inhibitor antidepressant
US4788195A (en) 1986-01-13 1988-11-29 American Cyanamid Company 4,5,6-substituted-N-(substituted-phenyl)-2-pyrimidinamines
US4792561A (en) 1986-05-29 1988-12-20 Syntex (U.S.A.) Inc. Carbostyril derivatives as combined thromboxane synthetase and cyclic-AMP phosphodiesterase inhibitors
EP0310550A1 (de) 1987-09-28 1989-04-05 Ciba-Geigy Ag Schädlingsbekämpfungsmittel
US4876252A (en) 1986-01-13 1989-10-24 American Cyanamid Company 4,5,6-substituted-N-(substituted-phenyl)-2-pyrimidinamines
US4897396A (en) 1988-06-03 1990-01-30 Ciba-Geigy Corporation 2-phenylamino pyrimidine derivatives and their uses as microbicides
US4921862A (en) 1986-05-29 1990-05-01 Syntex (U.S.A.) Inc. Carbostyril derivatives as combined thromboxane synthetase and cyclic-amp phosphodiesterase inhibitors
US4966622A (en) 1988-04-12 1990-10-30 Ciba-Geigy Corporation N-phenyl-N-pyrimidin-2-ylureas
US4971959A (en) 1987-04-14 1990-11-20 Warner-Lambert Company Trisubstituted phenyl analogs having activity for congestive heart failure
US4973690A (en) 1988-04-12 1990-11-27 Ciba-Geigy Corporation Novel ureas
US4987132A (en) 1987-02-20 1991-01-22 Yamanouchi Pharmaceutical Co., Ltd. Saturated heterocyclic carboxamide derivatives
JPH03127790A (ja) 1989-10-11 1991-05-30 Morishita Pharmaceut Co Ltd Ｎ―（１ｈ―テトラゾール―５―イル）―２―アニリノ―５―ピリミジンカルボキシアミド類及びその合成中間体
WO1991015451A1 (en) 1990-04-05 1991-10-17 Smithkline Beecham Pharma Gmbh Novel derivatives of phenyl-cycloalkanes and -cycloalkenes
WO1991016892A1 (en) 1990-04-27 1991-11-14 Rorer International (Holdings), Inc. Styryl compounds which inhibit egf receptor protein tyrosine kinase
WO1992000968A1 (en) 1990-07-10 1992-01-23 Smithkline Beecham Corporation Oxamides
DE4029650A1 (de) 1990-09-19 1992-03-26 Hoechst Ag 2-anilino-pyrimidine, verfahren zu ihrer herstellung, sie enthaltene mittel und ihre verwendung als fungizide
WO1992006085A1 (en) 1990-09-28 1992-04-16 Smith Kline & French Laboratories Limited Phenylpyridinol derivatives as medicaments
WO1992006963A1 (de) 1990-10-16 1992-04-30 Byk Gulden Lomberg Chemische Fabrik Gmbh Arylpyridazinone
WO1992007567A1 (en) 1990-11-06 1992-05-14 Smithkline Beecham Corporation Imidazolidinone compounds
US5124455A (en) 1990-08-08 1992-06-23 American Home Products Corporation Oxime-carbamates and oxime-carbonates as bronchodilators and anti-inflammatory agents
US5128358A (en) 1988-01-19 1992-07-07 Pfizer Inc. Aryl substituted nitrogen heterocyclic antidepressants
WO1992012961A1 (en) 1991-01-28 1992-08-06 Rhone Poulenc Rorer Limited Benzamides
WO1992019602A1 (de) 1991-04-26 1992-11-12 Byk Gulden Lomberg Chemische Fabrik Gmbh Neue pyridazine
WO1992019594A1 (en) 1991-05-02 1992-11-12 Smithkline Beecham Corporation Pyrrolidinones
US5164372A (en) 1989-04-28 1992-11-17 Fujisawa Pharmaceutical Company, Ltd. Peptide compounds having substance p antagonism, processes for preparation thereof and pharmaceutical composition comprising the same
US5175167A (en) 1990-02-09 1992-12-29 Basf Aktiengesellschaft Hetarylalkenes, their preparation and intermediates for their preparation and their use
US5177085A (en) 1990-12-13 1993-01-05 Sandoz Ltd. Dihydro-isoquinoline derivatives, processes for their production, pharmaceutical compositions containing them, and their use in treating asthma
WO1993010118A1 (de) 1991-11-11 1993-05-27 Knoll Atiengesellschaft Verfahren zur trennung von 5-methyl-tetrahydrofolsäure
US5236918A (en) 1989-04-17 1993-08-17 Byk Gulden Lomberg Chemische Fabrik Gmbh 6-aryl-3-cyanaminopyridazines, their preparation and use and medicaments containing them
WO1993019748A1 (en) 1992-04-02 1993-10-14 Smithkline Beecham Corporation Compounds useful for treating inflammatory diseases and for inhibiting production of tumor necrosis factor
US5274002A (en) 1987-04-14 1993-12-28 Warner-Lambert Company Trisubstituted phenyl analogs having activity for congestive heart failure
WO1994002465A1 (en) 1992-07-28 1994-02-03 Rhone-Poulenc Rorer Limited INHIBITORS OF c-AMP PHOSPHODIESTERASE AND TNF
US5298511A (en) 1991-10-03 1994-03-29 Imperial Chemical Industries Plc Alkanoic acid derivatives
WO1994010118A1 (en) 1992-10-23 1994-05-11 Celltech Limited Tri-substituted phenyl derivatives and processes for their preparation
WO1994012461A1 (en) 1992-12-02 1994-06-09 Pfizer Inc. Catechol diethers as selective pdeiv inhibitors
WO1994013361A1 (fr) 1992-12-07 1994-06-23 Blangy Gerard De Procede et dispositif de traitement et de valorisation de dechets transformant ceux-ci en materiaux non polluants et reutilisables
US5326898A (en) 1992-02-11 1994-07-05 Allergan, Inc. Substituted phenylethenyl compounds having retinoid-like biological activity
WO1994014742A1 (en) 1992-12-23 1994-07-07 Celltech Limited Tri-substituted phenyl derivatives as phosphodiesterase inhibitors
US5340827A (en) 1992-06-15 1994-08-23 Celltech, Limited Phenylcarboxamide compounds which have useful pharmaceutical activity
WO1994020446A1 (en) 1993-03-10 1994-09-15 Celltech Therapeutics Limited Trisubstituted phenyl derivatives as phosphodiesterase inhibitors and processes for their preparation
WO1994020455A1 (en) 1993-03-10 1994-09-15 Celltech Therapeutics Limited Styryl derivatives, their preparation and use as pde-iv inhibitors
WO1995004046A1 (en) 1993-07-28 1995-02-09 Rhone-Poulenc Rorer Limited Compounds as pde iv and tnf inhibitors
WO1995009851A1 (en) 1993-10-01 1995-04-13 Ciba-Geigy Ag Pharmacologically active pyrimidineamine derivatives and processes for the preparation thereof
WO1995009853A1 (en) 1993-10-01 1995-04-13 Ciba-Geigy Ag Pharmacologically active pyridine derivatives and processes for the preparation thereof
WO1995009847A1 (en) 1993-10-01 1995-04-13 Ciba-Geigy Ag Pyrimidineamine derivatives and processes for the preparation thereof
WO1995009852A1 (en) 1993-10-01 1995-04-13 Ciba-Geigy Ag Further pyrimidine derivatives and their preparation
WO1995017386A1 (en) 1993-12-22 1995-06-29 Celltech Therapeutics Limited An enantioselective process for the preparation of chiral triaryl derivatives and chiral intermediates for use therein
WO1995031451A1 (en) 1994-05-16 1995-11-23 Smithkline Beecham Corporation Novel compounds
WO1995033727A1 (en) 1994-06-06 1995-12-14 Pfizer Inc. Substituted pyrazoles having corticotropin-releasing factor (crf) antagonist activity
WO1996014843A2 (en) 1994-11-10 1996-05-23 Cor Therapeutics, Inc. Pharmaceutical pyrazole compositions useful as inhibitors of protein kinases
US5521184A (en) 1992-04-03 1996-05-28 Ciba-Geigy Corporation Pyrimidine derivatives and processes for the preparation thereof
US5550137A (en) 1992-06-15 1996-08-27 Celltech Therapeutics Limited Phenylaminocarbonyl derivatives
US5580888A (en) 1992-12-23 1996-12-03 Celltech Therapeutics Limited Styryl derivatives as anti-inflammatory agents
US5593997A (en) 1995-05-23 1997-01-14 Pfizer Inc. 4-aminopyrazolo(3-,4-D)pyrimidine and 4-aminopyrazolo-(3,4-D)pyridine tyrosine kinase inhibitors
WO1997009325A1 (en) 1995-09-01 1997-03-13 Signal Pharmaceuticals, Inc. Pyrimidine carboxylates and related compounds and methods for treating inflammatory conditions
US5622977A (en) 1992-12-23 1997-04-22 Celltech Therapeutics Limited Tri-substituted (aryl or heteroaryl) derivatives and pharmaceutical compositions containing the same
US5691376A (en) 1994-02-17 1997-11-25 American Home Products Corporation Substituted biphenyl derivatives
US5693659A (en) 1994-06-23 1997-12-02 Celltech Therapeutics Limited Substituted oxime derivatives and processes for their preparation
US5698711A (en) 1991-01-28 1997-12-16 Rhone-Poulenc Rorer Limited Compounds containing phenyl linked to aryl or heteroaryl by an aliphatic- or heteroatom-containing linking group
US5716967A (en) 1993-11-26 1998-02-10 Pfizer Inc. Isoxazoline compounds as antiinflammatory agents
US5753663A (en) 1995-10-02 1998-05-19 Syntex (U.S.A.) Inc. Pyrimidine derivatives
US5776958A (en) 1993-12-22 1998-07-07 Celltech Therapeutics, Limited Trisubstituted phenyl derivatives and processes for their preparation
US5780478A (en) 1994-06-22 1998-07-14 Celltech Therapeutics, Limited Tetra-substituted phenyl derivatives
US5780477A (en) 1994-06-22 1998-07-14 Celltech Therapeutics, Limited Trisubstituted phenyl derivatives and processes for their preparation
US5786354A (en) 1994-06-21 1998-07-28 Celltech Therapeutics, Limited Tri-substituted phenyl derivatives and processes for their preparation
US5798373A (en) 1995-12-21 1998-08-25 Celltech Therapeutics, Limited Tri-substituted phenyl derivatives useful as PDE IV inhibitors
US5849770A (en) 1995-12-21 1998-12-15 Celltech Therapeutics Ltd. Tri-substituted phenyl derivatives useful as PDE IV inhibitors
US5851784A (en) 1994-12-23 1998-12-22 Celltech Therapeutics, Limited Human phosphodiesterase type IVC, and its production and use
US5859034A (en) 1996-12-04 1999-01-12 Celltech Therapeutics, Limited Tri-substituted phenyl compounds which have useful pharmaceutical activity
US5866593A (en) 1993-12-22 1999-02-02 Celltech Therapeutics Ltd. Trisubstituted phenyl derivatives and processes for their preparation
US5891896A (en) 1995-12-21 1999-04-06 Celltech Therapeutics Ltd. Tri-substituted phenyl derivatives useful as PDE IV inhibitors
US5922741A (en) 1996-04-24 1999-07-13 Celltech Therapeutics Ltd. 5-aminopyrazoles useful as tyrosine kinase inhibitors
US5958935A (en) * 1995-11-20 1999-09-28 Celltech Therapeutics Limited Substituted 2-anilinopyrimidines useful as protein kinase inhibitors
US6048866A (en) 1997-03-14 2000-04-11 Celltech Therapeutics, Limited Substituted 2-anilinopryimidines useful as protein kinase inhibitors
US6093716A (en) 1996-09-16 2000-07-25 Celltech Therapeutics, Limited Substituted 2-pyrimidineamines and processes for their preparation
US20030134838A1 (en) 2001-10-17 2003-07-17 Boehringer Ingelheim Pharma Kg Trisubstituted pyrimidines
US20030171359A1 (en) 2001-10-17 2003-09-11 Boehringer Ingelheim Pharma Kg Pyrimidine derivatives
US20040029902A1 (en) 2002-02-01 2004-02-12 Rajinder Singh 2,4-Pyrimidinediamine compounds and their uses

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5164078A (en) * 1989-12-28 1992-11-17 Chevron Research And Technology Company Process for removal of calcium from a hydrocarbon feedstock
US5385963A (en) * 1992-01-30 1995-01-31 Gencorp Inc. Unsaturated polyester-modified flexible copolymers for use in sheet molding compositions
RU2130453C1 (ru) 1992-12-17 1999-05-20 Пфайзер Инк. Замещенные пиразолы, фармацевтическая композиция на их основе, способ лечения, промежуточный продукт
US5785354A (en) * 1996-05-06 1998-07-28 Temtec, Inc. Self-expiring identification band
JP2001509805A (ja) * 1997-02-05 2001-07-24 ワーナー−ランバート・コンパニー 細胞増殖阻害剤としてのピリド〔２，３−ｄ〕ピリミジンおよび４−アミノピリミジン
GB9806739D0 (en) * 1998-03-28 1998-05-27 Univ Newcastle Ventures Ltd Cyclin dependent kinase inhibitors
GB9828511D0 (en) * 1998-12-24 1999-02-17 Zeneca Ltd Chemical compounds
GB9905075D0 (en) * 1999-03-06 1999-04-28 Zeneca Ltd Chemical compounds
GB9919778D0 (en) * 1999-08-21 1999-10-27 Zeneca Ltd Chemical compounds
GB0016877D0 (en) * 2000-07-11 2000-08-30 Astrazeneca Ab Chemical compounds
PL367130A1 (en) * 2001-05-29 2005-02-21 Schering Aktiengesellschaft Cdk inhibiting pyrimidines, production thereof and their use as medicaments
MXPA05005547A (es) * 2002-11-28 2005-07-26 Schering Ag Pirimidinas inhibidoras de chk, pdk y akt, su produccion y uso como agentes farmaceuticos.
DE10349423A1 (de) * 2003-10-16 2005-06-16 Schering Ag Sulfoximinsubstituierte Parimidine als CDK- und/oder VEGF-Inhibitoren, deren Herstellung und Verwendung als Arzneimittel

Patent Citations (100)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3947467A (en) 1973-08-02 1976-03-30 Eli Lilly And Company 3-(5-Nitro-2-imidazolyl) pyrazoles
US4015017A (en) 1974-01-15 1977-03-29 Laboratoires Pharmascience Certain biphenyl derivatives used to treat disorders caused by increased capillary permeability
US4012495A (en) 1974-03-20 1977-03-15 Schering Aktiengesellschaft 4-(Polyalkoxyphenyl)-2-pyrrolidones
US4193926A (en) 1974-03-20 1980-03-18 Schering Aktiengesellschaft 4-(Polyalkoxy phenyl)-2-pyrrolidones
US4153713A (en) 1975-09-18 1979-05-08 Schering Aktiengesellschaft 4-(Polyalkoxyphenyl)-2-pyrrolidones (II)
US4303649A (en) 1978-06-15 1981-12-01 Imperial Chemical Industries Limited 1-Phenyl-2-aminoethanol derivatives
US4548940A (en) 1982-12-23 1985-10-22 Smith Kline & French Laboratories Limited Pyridylaminoalkylaminopyrimidones useful as histamine H1 -antagonists
US4694009A (en) 1984-06-25 1987-09-15 Ciba-Geigy Corporation Pesticidal compositions
US4988704A (en) 1985-10-30 1991-01-29 Kumiai Chemical Industry Co., Ltd. Pyrimidine derivative, process for preparing same and argicultural or horticultural fungicidal composition containing same
EP0224339A2 (en) 1985-10-30 1987-06-03 Kumiai Chemical Industry Co., Ltd. Pyrimidine derivative, process for preparing same and agricultural or horticultural fungicidal composition containing same
US4788195A (en) 1986-01-13 1988-11-29 American Cyanamid Company 4,5,6-substituted-N-(substituted-phenyl)-2-pyrimidinamines
US4876252A (en) 1986-01-13 1989-10-24 American Cyanamid Company 4,5,6-substituted-N-(substituted-phenyl)-2-pyrimidinamines
WO1987006576A1 (en) 1986-04-29 1987-11-05 Pfizer Inc. Calcium independent camp phosphodiesterase inhibitor antidepressant
US4792561A (en) 1986-05-29 1988-12-20 Syntex (U.S.A.) Inc. Carbostyril derivatives as combined thromboxane synthetase and cyclic-AMP phosphodiesterase inhibitors
US4921862A (en) 1986-05-29 1990-05-01 Syntex (U.S.A.) Inc. Carbostyril derivatives as combined thromboxane synthetase and cyclic-amp phosphodiesterase inhibitors
US4987132A (en) 1987-02-20 1991-01-22 Yamanouchi Pharmaceutical Co., Ltd. Saturated heterocyclic carboxamide derivatives
US5274002A (en) 1987-04-14 1993-12-28 Warner-Lambert Company Trisubstituted phenyl analogs having activity for congestive heart failure
US4971959A (en) 1987-04-14 1990-11-20 Warner-Lambert Company Trisubstituted phenyl analogs having activity for congestive heart failure
EP0310550A1 (de) 1987-09-28 1989-04-05 Ciba-Geigy Ag Schädlingsbekämpfungsmittel
US5128358A (en) 1988-01-19 1992-07-07 Pfizer Inc. Aryl substituted nitrogen heterocyclic antidepressants
US4966622A (en) 1988-04-12 1990-10-30 Ciba-Geigy Corporation N-phenyl-N-pyrimidin-2-ylureas
US4973690A (en) 1988-04-12 1990-11-27 Ciba-Geigy Corporation Novel ureas
US5159078A (en) 1988-04-12 1992-10-27 Ciba-Geigy Corporation 2-analino pyrimidine compounds
US4897396A (en) 1988-06-03 1990-01-30 Ciba-Geigy Corporation 2-phenylamino pyrimidine derivatives and their uses as microbicides
US5236918A (en) 1989-04-17 1993-08-17 Byk Gulden Lomberg Chemische Fabrik Gmbh 6-aryl-3-cyanaminopyridazines, their preparation and use and medicaments containing them
US5164372A (en) 1989-04-28 1992-11-17 Fujisawa Pharmaceutical Company, Ltd. Peptide compounds having substance p antagonism, processes for preparation thereof and pharmaceutical composition comprising the same
JPH03127790A (ja) 1989-10-11 1991-05-30 Morishita Pharmaceut Co Ltd Ｎ―（１ｈ―テトラゾール―５―イル）―２―アニリノ―５―ピリミジンカルボキシアミド類及びその合成中間体
US5175167A (en) 1990-02-09 1992-12-29 Basf Aktiengesellschaft Hetarylalkenes, their preparation and intermediates for their preparation and their use
WO1991015451A1 (en) 1990-04-05 1991-10-17 Smithkline Beecham Pharma Gmbh Novel derivatives of phenyl-cycloalkanes and -cycloalkenes
WO1991016892A1 (en) 1990-04-27 1991-11-14 Rorer International (Holdings), Inc. Styryl compounds which inhibit egf receptor protein tyrosine kinase
WO1992000968A1 (en) 1990-07-10 1992-01-23 Smithkline Beecham Corporation Oxamides
US5124455A (en) 1990-08-08 1992-06-23 American Home Products Corporation Oxime-carbamates and oxime-carbonates as bronchodilators and anti-inflammatory agents
DE4029650A1 (de) 1990-09-19 1992-03-26 Hoechst Ag 2-anilino-pyrimidine, verfahren zu ihrer herstellung, sie enthaltene mittel und ihre verwendung als fungizide
WO1992006085A1 (en) 1990-09-28 1992-04-16 Smith Kline & French Laboratories Limited Phenylpyridinol derivatives as medicaments
WO1992006963A1 (de) 1990-10-16 1992-04-30 Byk Gulden Lomberg Chemische Fabrik Gmbh Arylpyridazinone
WO1992007567A1 (en) 1990-11-06 1992-05-14 Smithkline Beecham Corporation Imidazolidinone compounds
US5177085A (en) 1990-12-13 1993-01-05 Sandoz Ltd. Dihydro-isoquinoline derivatives, processes for their production, pharmaceutical compositions containing them, and their use in treating asthma
US5698711A (en) 1991-01-28 1997-12-16 Rhone-Poulenc Rorer Limited Compounds containing phenyl linked to aryl or heteroaryl by an aliphatic- or heteroatom-containing linking group
WO1992012961A1 (en) 1991-01-28 1992-08-06 Rhone Poulenc Rorer Limited Benzamides
WO1992019602A1 (de) 1991-04-26 1992-11-12 Byk Gulden Lomberg Chemische Fabrik Gmbh Neue pyridazine
WO1992019594A1 (en) 1991-05-02 1992-11-12 Smithkline Beecham Corporation Pyrrolidinones
US5298511A (en) 1991-10-03 1994-03-29 Imperial Chemical Industries Plc Alkanoic acid derivatives
WO1993010118A1 (de) 1991-11-11 1993-05-27 Knoll Atiengesellschaft Verfahren zur trennung von 5-methyl-tetrahydrofolsäure
US5326898A (en) 1992-02-11 1994-07-05 Allergan, Inc. Substituted phenylethenyl compounds having retinoid-like biological activity
WO1993019748A1 (en) 1992-04-02 1993-10-14 Smithkline Beecham Corporation Compounds useful for treating inflammatory diseases and for inhibiting production of tumor necrosis factor
US5521184A (en) 1992-04-03 1996-05-28 Ciba-Geigy Corporation Pyrimidine derivatives and processes for the preparation thereof
US5340827A (en) 1992-06-15 1994-08-23 Celltech, Limited Phenylcarboxamide compounds which have useful pharmaceutical activity
US6096747A (en) 1992-06-15 2000-08-01 Celltech Therapeutics Limited Phenylaminocarbonyl derivatives and processes for their preparation
US5550137A (en) 1992-06-15 1996-08-27 Celltech Therapeutics Limited Phenylaminocarbonyl derivatives
WO1994002465A1 (en) 1992-07-28 1994-02-03 Rhone-Poulenc Rorer Limited INHIBITORS OF c-AMP PHOSPHODIESTERASE AND TNF
US5491147A (en) 1992-10-23 1996-02-13 Celltech, Limited Tri-substituted phenyl derivatives and their use in pharmaceutical compositions and methods of treatment
US6080790A (en) 1992-10-23 2000-06-27 Celltech Therapeutics, Limited Tri-substituted phenyl derivatives and processes for their preparations
WO1994010118A1 (en) 1992-10-23 1994-05-11 Celltech Limited Tri-substituted phenyl derivatives and processes for their preparation
US5674880A (en) 1992-10-23 1997-10-07 Celltech Therapeutics Limited Tri-substituted phenyl derivatives and processes for their preparation
WO1994012461A1 (en) 1992-12-02 1994-06-09 Pfizer Inc. Catechol diethers as selective pdeiv inhibitors
WO1994013361A1 (fr) 1992-12-07 1994-06-23 Blangy Gerard De Procede et dispositif de traitement et de valorisation de dechets transformant ceux-ci en materiaux non polluants et reutilisables
WO1994014742A1 (en) 1992-12-23 1994-07-07 Celltech Limited Tri-substituted phenyl derivatives as phosphodiesterase inhibitors
US5622977A (en) 1992-12-23 1997-04-22 Celltech Therapeutics Limited Tri-substituted (aryl or heteroaryl) derivatives and pharmaceutical compositions containing the same
US5580888A (en) 1992-12-23 1996-12-03 Celltech Therapeutics Limited Styryl derivatives as anti-inflammatory agents
WO1994020446A1 (en) 1993-03-10 1994-09-15 Celltech Therapeutics Limited Trisubstituted phenyl derivatives as phosphodiesterase inhibitors and processes for their preparation
WO1994020455A1 (en) 1993-03-10 1994-09-15 Celltech Therapeutics Limited Styryl derivatives, their preparation and use as pde-iv inhibitors
US5739144A (en) 1993-03-10 1998-04-14 Celltech Therapeutics Limited Trisubstituted phenyl derivatives
US5723460A (en) 1993-03-10 1998-03-03 Celltech Therapeutics Limited Cyclo (alkyl and alkenyl) phenyl-alkenylyl heteroaryl compounds and pharmaceutical compositions containing same
US5633257A (en) 1993-03-10 1997-05-27 Celltech Therapeutics Limited Cyclo(alkyl and alkenyl)phenyl-alkenylyl(aryl and heteroaryl)compounds and pharmaceutical compositions containing them
WO1995004046A1 (en) 1993-07-28 1995-02-09 Rhone-Poulenc Rorer Limited Compounds as pde iv and tnf inhibitors
WO1995009847A1 (en) 1993-10-01 1995-04-13 Ciba-Geigy Ag Pyrimidineamine derivatives and processes for the preparation thereof
WO1995009851A1 (en) 1993-10-01 1995-04-13 Ciba-Geigy Ag Pharmacologically active pyrimidineamine derivatives and processes for the preparation thereof
US5728708A (en) 1993-10-01 1998-03-17 Novartis Corporation Pharmacologically active pyridine derivatives and processes for the preparation thereof
WO1995009852A1 (en) 1993-10-01 1995-04-13 Ciba-Geigy Ag Further pyrimidine derivatives and their preparation
WO1995009853A1 (en) 1993-10-01 1995-04-13 Ciba-Geigy Ag Pharmacologically active pyridine derivatives and processes for the preparation thereof
US5716967A (en) 1993-11-26 1998-02-10 Pfizer Inc. Isoxazoline compounds as antiinflammatory agents
WO1995017386A1 (en) 1993-12-22 1995-06-29 Celltech Therapeutics Limited An enantioselective process for the preparation of chiral triaryl derivatives and chiral intermediates for use therein
US5776958A (en) 1993-12-22 1998-07-07 Celltech Therapeutics, Limited Trisubstituted phenyl derivatives and processes for their preparation
US5608070A (en) 1993-12-22 1997-03-04 Celltech Therapeutics Limited Enantioselective process for the preparation of chiral triaryl derivatives and chiral intermediates for use therein
US5866593A (en) 1993-12-22 1999-02-02 Celltech Therapeutics Ltd. Trisubstituted phenyl derivatives and processes for their preparation
US5691376A (en) 1994-02-17 1997-11-25 American Home Products Corporation Substituted biphenyl derivatives
WO1995031451A1 (en) 1994-05-16 1995-11-23 Smithkline Beecham Corporation Novel compounds
WO1995033727A1 (en) 1994-06-06 1995-12-14 Pfizer Inc. Substituted pyrazoles having corticotropin-releasing factor (crf) antagonist activity
US5786354A (en) 1994-06-21 1998-07-28 Celltech Therapeutics, Limited Tri-substituted phenyl derivatives and processes for their preparation
US5780478A (en) 1994-06-22 1998-07-14 Celltech Therapeutics, Limited Tetra-substituted phenyl derivatives
US5780477A (en) 1994-06-22 1998-07-14 Celltech Therapeutics, Limited Trisubstituted phenyl derivatives and processes for their preparation
US5693659A (en) 1994-06-23 1997-12-02 Celltech Therapeutics Limited Substituted oxime derivatives and processes for their preparation
WO1996014843A2 (en) 1994-11-10 1996-05-23 Cor Therapeutics, Inc. Pharmaceutical pyrazole compositions useful as inhibitors of protein kinases
US5851784A (en) 1994-12-23 1998-12-22 Celltech Therapeutics, Limited Human phosphodiesterase type IVC, and its production and use
US5593997A (en) 1995-05-23 1997-01-14 Pfizer Inc. 4-aminopyrazolo(3-,4-D)pyrimidine and 4-aminopyrazolo-(3,4-D)pyridine tyrosine kinase inhibitors
WO1997009325A1 (en) 1995-09-01 1997-03-13 Signal Pharmaceuticals, Inc. Pyrimidine carboxylates and related compounds and methods for treating inflammatory conditions
US5753663A (en) 1995-10-02 1998-05-19 Syntex (U.S.A.) Inc. Pyrimidine derivatives
US5958935A (en) * 1995-11-20 1999-09-28 Celltech Therapeutics Limited Substituted 2-anilinopyrimidines useful as protein kinase inhibitors
US6235746B1 (en) 1995-11-20 2001-05-22 Celltech Therapeutics, Limited Substituted 2-anilinopyrimidines useful as protein kinase inhibitors
US5891896A (en) 1995-12-21 1999-04-06 Celltech Therapeutics Ltd. Tri-substituted phenyl derivatives useful as PDE IV inhibitors
US5849770A (en) 1995-12-21 1998-12-15 Celltech Therapeutics Ltd. Tri-substituted phenyl derivatives useful as PDE IV inhibitors
US5798373A (en) 1995-12-21 1998-08-25 Celltech Therapeutics, Limited Tri-substituted phenyl derivatives useful as PDE IV inhibitors
US5922741A (en) 1996-04-24 1999-07-13 Celltech Therapeutics Ltd. 5-aminopyrazoles useful as tyrosine kinase inhibitors
US6093716A (en) 1996-09-16 2000-07-25 Celltech Therapeutics, Limited Substituted 2-pyrimidineamines and processes for their preparation
US5859034A (en) 1996-12-04 1999-01-12 Celltech Therapeutics, Limited Tri-substituted phenyl compounds which have useful pharmaceutical activity
US6048866A (en) 1997-03-14 2000-04-11 Celltech Therapeutics, Limited Substituted 2-anilinopryimidines useful as protein kinase inhibitors
US6337335B1 (en) 1997-03-14 2002-01-08 Celltech Therapeutics Limited Substituted 2-anilinopyrimidines useful as protein kinase inhibitors
US20030134838A1 (en) 2001-10-17 2003-07-17 Boehringer Ingelheim Pharma Kg Trisubstituted pyrimidines
US20030171359A1 (en) 2001-10-17 2003-09-11 Boehringer Ingelheim Pharma Kg Pyrimidine derivatives
US20040029902A1 (en) 2002-02-01 2004-02-12 Rajinder Singh 2,4-Pyrimidinediamine compounds and their uses

Non-Patent Citations (18)

* Cited by examiner, † Cited by third party
Title
Amendment and IDS filed Dec. 14, 2005 in U.S. Appl. No. 10/271,763 (filed Oct. 16, 2002); Examiner Deepak R. Rao.
D. Boschelli et al., "Synthesis and Tyrosine Kinase Inhibitory Activity Of A Series of 2-Amino-8-H-Pyridoä2, 3-Düpyrimidines: Identification of Potent, Selective Platelet-Derived Growth Factor Receptor Tyrosine Kinase Inhibitors," Journal of Medicinal Chemistry, American Chemical Society, Washington, US, Bd. 41, Nr. 22, 1998, pp. 4365-4377, XP002191993.
Database Chemcats Online! Chemical Abstracts Service, Columbus, OH, US; Jan. 21, 2002, retrieved from STN, XP002210161, Order No. F0487-0047 & "Ambinter Exploratory Library," Ambinter, F-75016 Paris.
Database Chemcats Online! Chemical Abstracts Services, Columbus, OH, US; retrieved fro STN XP002210162 Order No. CD207267, CD207266 & "Oak Samples Product List" Oct. 8, 2001, Oak Samples Ltd., 03680 KIEV-142, Ukraine.
Database Crossfire Beilstein Online! Beilstein Institut zur Förderung der Chemischen Wissenschaften, Frankfurt am Main, DE; Database Accession No. BRN 249340, 265505, XP002210163 &1. Naito et al., Chem. Pharm. Bull., Bd. 6, 1958, pp. 338-341.
Office Action dated Jan. 13, 2006 in U.S. Appl. No. 11/007,923 (filed Dec. 9, 2004); Examiner Kahsay Habte.
Office Action dated Mar. 10, 2006 in U.S. Appl. No. 10/271,763 (filed Oct. 16, 2002); Examiner Deepak R. Rao.
Office Action of Jul. 14, 2005 in 10/271,763.
Patent Abstracts of Japan, Patent No. 031277790 A, May 30, 1991.
PCT Search Report for App. No. PCT/EP02/05669 date Dec. 9, 2002.
Response filed by Dahmann et al. in 10/271,763, (US2003/0171359) on Apr. 19, 2005.
S. Ding et al., "A Combunatorial Scaffold Approach Toward Kinase-Directed Heterocycle Libraries," Journal of the American Chemical Society, 2002,124(8), pp. 1594-1596, XP002210160.
U.S. Appl. No. 60/330,128, filed Oct. 17, 2001.
U.S. Appl. No. 60/330,145, filed Oct. 17, 2001.
U.S. Appl. No. 60/353,267, filed Feb. 1, 2002.
U.S. Appl. No. 60/353,333, filed Feb. 1, 2002.
U.S. Appl. No. 60/399,673, filed Jul. 29, 2002.
U.S. Appl. No. 60/434,277, filed Dec. 17, 2002.

Cited By (58)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080039447A1 (en) * 2001-05-29 2008-02-14 Thomas Brumby CDK-Inhibitory pyrimidines, their production and use as pharmaceutical agents
US7598260B2 (en) * 2001-05-29 2009-10-06 Bayer Schering Pharma Aktiengesellschaft CDK-inhibitory pyrimidines, their production and use as pharmaceutical agents
US7803939B2 (en) 2002-02-01 2010-09-28 Rigel Pharmaceuticals, Inc. 2,4-pyrimidinediamine compounds and their uses
US20090082567A1 (en) * 2002-02-01 2009-03-26 Rigel Pharmaceuticals, Inc. 2,4-pyrimidinediamine compounds and their uses
US8334296B2 (en) 2002-02-01 2012-12-18 Rigel Pharmaceuticals, Inc. 2,4-pyrimidinediamine compounds and their uses
US7642351B2 (en) 2002-02-01 2010-01-05 Rogel Pharmaceuticals, Inc. 2,4-Pyrimidinediamine compounds and their uses
US20070293521A1 (en) * 2002-02-01 2007-12-20 Rigel Pharmaceuticals, Inc. 2,4-pyrimidinediamine compounds and their uses
US8148525B2 (en) 2002-02-01 2012-04-03 Rigel Pharmaceuticals, Inc. 2,4-pyrimidinediamine compounds and their uses
US20090171085A1 (en) * 2002-02-01 2009-07-02 Rigel Pharmaceuticals, Inc. 2,4-pyrimidinediamine compounds and their uses
US20090156622A1 (en) * 2002-02-01 2009-06-18 Rigel Pharmaceuticals, Inc. 2,4-pyrimidinediamine compounds and their uses
US7485724B2 (en) 2002-02-01 2009-02-03 Rigel Pharmaceuticals, Inc. 2,4-pyrimidinediamine compounds and their uses
US7820819B2 (en) 2002-02-01 2010-10-26 Rigel Pharmaceuticals, Inc. 2,4-pyrimidinediamine compounds and their uses
US7498435B2 (en) 2002-02-01 2009-03-03 Rigel Pharmaceuticals, Inc. 2,4-pyrimidinediamine compounds and their uses
US7655797B2 (en) 2002-02-01 2010-02-02 Rigel Pharmaceuticals, Inc. Intermediates for making 2,4-pyrimidinediamine compounds
US7812029B1 (en) 2002-07-29 2010-10-12 Rigel Pharmaceuticals, Inc. Methods of treating or preventing autoimmune diseases with 2,4-pyrimidinediamine compounds
US20070299095A1 (en) * 2002-07-29 2007-12-27 Rigel Pharmaceuticals, Inc. Methods of treating or preventing autoimmune diseases with 2,4-pyrimidinediamine compounds
US7825116B2 (en) 2002-07-29 2010-11-02 Rigel Pharmaceuticals, Inc. N2, N4-bis-aryl-5-fluoro-2,4-pyrimidinediamines
US20100125069A1 (en) * 2002-07-29 2010-05-20 Rigel Pharmaceuticals Inc. Methods of Treating or Preventing Autoimmune Diseases with 2,4-Pyrimidinediamine Compounds
US8158621B2 (en) 2002-07-29 2012-04-17 Rigel Pharmaceuticals, Inc. Methods of treating or preventing autoimmune diseases with 2,4-pyrimidinediamine compounds
US7741336B2 (en) 2002-12-20 2010-06-22 Pfizer Inc. Pyrimidine derivatives for the treatment of abnormal cell growth
US20080300234A1 (en) * 2002-12-20 2008-12-04 Pfizer Inc. Pyrimidine derivatives for the treatment of abnormal cell growth
US7674796B2 (en) 2002-12-20 2010-03-09 Pfizer Inc. Pyrimidine derivatives for the treatment of abnormal cell growth
US20080182840A1 (en) * 2002-12-20 2008-07-31 Pfizer Inc Pyrimidine derivatives for the treatment of abnormal cell growth
US20090062270A1 (en) * 2004-11-24 2009-03-05 Rigel Pharmaceuticals, Inc. Spiro 2,4 pyrimidinediamine compounds and their uses
US7851480B2 (en) 2004-11-24 2010-12-14 Rigel Pharmaceuticals, Inc. Spiro 2,4-pyrimidinediamine compounds and their uses
US9532998B2 (en) 2005-01-19 2017-01-03 Rigel Pharmaceuticals, Inc. Prodrugs of 2,4-pyrimidinediamine compounds and their uses
US7538108B2 (en) 2005-01-19 2009-05-26 Rigel Pharmaceuticals, Inc. Prodrugs of 2,4-pyrimidinediamine compounds and their uses
US20090124580A1 (en) * 2005-01-19 2009-05-14 Rigel Pharmaceuticals, Inc. Prodrugs of 2,4-pyrimidinediamine compounds and their uses
US20060234983A1 (en) * 2005-01-19 2006-10-19 Rigel Pharmaceuticals, Inc. Prodrugs of 2,4-pyrimidinediamine compounds and their uses
US10577381B2 (en) 2005-01-19 2020-03-03 Rigel Pharmaceuticals, Inc. Prodrugs of 2,4-pyrimidinediamine compounds and their uses
US8476263B2 (en) 2005-01-19 2013-07-02 Rigel Pharmaceuticals, Inc. Prodrugs of 2,4-pyrimidinediamine compounds and their uses
US7563892B1 (en) 2005-01-19 2009-07-21 Rigel Pharmaceuticals, Inc. Prodrugs of 2,4 pyrimidinediamine compounds and their uses
US9266912B2 (en) 2005-01-19 2016-02-23 Rigel Pharmaceuticals, Inc. Prodrugs of 2,4-pyrimidinediamine compounds and their uses
US7989448B2 (en) 2005-01-19 2011-08-02 Rigel Pharmaceuticals, Inc. Prodrugs of 2,4-pyrimidinediamine compounds and their uses
US7449458B2 (en) 2005-01-19 2008-11-11 Rigel Pharmaceuticals, Inc. Prodrugs of 2,4-pyrimidinediamine compounds and their uses
US8785437B2 (en) 2005-01-19 2014-07-22 Rigel Pharmaceuticals, Inc. Prodrugs of 2,4-pyrimidinediamine compounds and their uses
US8211889B2 (en) 2005-01-19 2012-07-03 Rigel Pharmaceuticals, Inc. Prodrugs of 2,4-pyrimidinediamine compounds and their uses
US8211888B2 (en) 2005-01-19 2012-07-03 Rigel Pharmaceuticals, Inc. Prodrugs of 2,4-pyrimidinediamine compounds and their uses
US9248190B2 (en) 2005-06-08 2016-02-02 Rigel Pharmaceuticals, Inc. Compositions and methods for inhibition of the JAK pathway
US9593082B2 (en) 2005-06-08 2017-03-14 Rigel Pharmaceuticals, Inc. Compositions and methods for inhibition of the JAK pathway
US8399472B2 (en) 2005-06-08 2013-03-19 Rigel Pharmaceuticals, Inc. Compositions and methods for inhibition of the JAK pathway
US8415365B2 (en) 2005-06-08 2013-04-09 Rigel Pharmaceuticals, Inc. Compositions and methods for inhibition of the JAK pathway
US11827628B2 (en) 2005-06-08 2023-11-28 Rigel Pharmaceuticals, Inc. Compositions and methods for inhibition of the JAK pathway
US20080221089A1 (en) * 2005-06-08 2008-09-11 Rigel Pharmaceuticals, Inc. Compositions and methods for inhibition of the jak pathway
US8815848B2 (en) 2005-06-08 2014-08-26 Rigel Pharmaceuticals, Inc. Compositions and methods for inhibition of the JAK pathway
US11198689B2 (en) 2005-06-08 2021-12-14 Rigel Pharmaceuticals, Inc. Compositions and methods for inhibition of the JAK pathway
US20090041786A1 (en) * 2005-06-08 2009-02-12 Rigel Pharmaceuticals, Inc. Compositions and methods for inhibition of the jak pathway
US10421752B2 (en) 2005-06-08 2019-09-24 Rigel Pharmaceuticals, Inc. Compositions and methods for inhibition of the JAK pathway
US9732073B2 (en) 2005-06-08 2017-08-15 Rigel Pharmaceuticals, Inc. Compositions and methods for inhibition of the JAK pathway
US20080306099A1 (en) * 2005-06-08 2008-12-11 Rigel Pharmaceuticals, Inc. Compositions and methods for inhibition of the jak pathway
US20090304694A1 (en) * 2006-01-27 2009-12-10 Amgen Inc. Ang2 and Vegf Inhibitor Combinations
US11667611B2 (en) 2006-02-24 2023-06-06 Rigel Pharmaceuticals, Inc. Compositions and methods for inhibition of the JAK pathway
US20080152712A1 (en) * 2006-09-26 2008-06-26 David Monteith Rapidly disintegrating lyophilized oral formulations of a thrombin receptor antagonist
US20110159019A1 (en) * 2008-09-01 2011-06-30 Akira Tanaka 2,4-diaminopyrimidine compound
US8927547B2 (en) 2010-05-21 2015-01-06 Noviga Research Ab Pyrimidine derivatives
US8354420B2 (en) 2010-06-04 2013-01-15 Genentech, Inc. Aminopyrimidine derivatives as LRRK2 inhibitors
US8815882B2 (en) 2010-11-10 2014-08-26 Genentech, Inc. Pyrazole aminopyrimidine derivatives as LRRK2 modulators
US9006241B2 (en) 2011-03-24 2015-04-14 Noviga Research Ab Pyrimidine derivatives

Also Published As

Publication number Publication date
KR100874791B1 (ko) 2008-12-18
PL367130A1 (en) 2005-02-21
NO20035298D0 (no) 2003-11-28
MEP13408A (en) 2010-06-10
EP1392662A1 (de) 2004-03-03
ATE420077T1 (de) 2009-01-15
NO327129B1 (no) 2009-04-27
DE50213202D1 (de) 2009-02-26
AR036035A1 (es) 2004-08-04
AU2002312933B2 (en) 2007-12-06
US20040224966A1 (en) 2004-11-11
US7598260B2 (en) 2009-10-06
RS94703A (en) 2007-02-05
JP2004535414A (ja) 2004-11-25
CN1633419A (zh) 2005-06-29
US20040102630A1 (en) 2004-05-27
MXPA03010810A (es) 2004-03-22
EP1392662B1 (de) 2009-01-07
KR20040030645A (ko) 2004-04-09
BR0209774A (pt) 2004-06-01
CN100480242C (zh) 2009-04-22
RU2330024C2 (ru) 2008-07-27
JP4291135B2 (ja) 2009-07-08
RU2003136080A (ru) 2005-05-20
ES2320204T3 (es) 2009-05-20
US7291624B2 (en) 2007-11-06
CA2449118A1 (en) 2002-12-05
HRP20031081A2 (en) 2005-10-31
IL159120A0 (en) 2004-05-12
CO5540316A2 (es) 2005-07-29
NZ529654A (en) 2005-12-23
WO2002096888A1 (de) 2002-12-05
US20080039447A1 (en) 2008-02-14

Similar Documents

Publication Publication Date Title
US7235561B2 (en) Compound and a composition including such a compound
US7288547B2 (en) CDK-inhibitory 2-heteroaryl-pyrimidines, their production and use as pharmaceutical agents
US7312225B2 (en) Macrocyclic pyrimidines, their production and use as pharmaceutical agents
US7504410B2 (en) Chk-, Pdk- and Akt-inhibitory pyrimidines, their production and use as pharmaceutical agents
US6747046B2 (en) Substituted N-(1,4,5,6-tetrahydro-cyclopentapyrazol-3-yl) derivatives, their production and use as pharmaceutical agents
US7338958B2 (en) Sulfoximine-substituted pyrimidines as CDK-and/or VEGF inhibitors, their production and use as pharmaceutical agents
US7825128B2 (en) Sulfoximine-substituted pyrimidines, processes for production thereof and use thereof as drugs
JP2005526765A (ja) Ｃｄｋ−阻害性２−ヘテロアリール−ピリミジン類、それらの生成及び医薬としての使用
US7456191B2 (en) N-Aryl-sulfoximine-substituted pyrimidines as CDK-and/or VEGF inhibitors, their production and use as pharmaceutical agents
US20060111378A1 (en) Substituted 2-anilinopyrimidines as cell-cycle-kinase or receptor-tyrosine-kinase inhibitors, their production and use as pharmaceutical agents
US20040186288A1 (en) 3,5-Diamino-1,2,4-triazoles as kinase inhibitors
ZA200309824B (en) CDK inhibiting pyrimidines, production thereof and their use as medicaments

Legal Events

Date Code Title Description
AS Assignment

Owner name: SCHERING AG, GERMANY

Free format text: RESUBMISSION OF ASSIGNMENT, DOCUMENT ID NO. 102279765. THE DATES ARE ACTUALLY AS IDENTIFIED BELOW;ASSIGNORS:BRUMBY, THOMAS;JAUTELAT, ROLF;PRIEN, OLAF;AND OTHERS;REEL/FRAME:013946/0895;SIGNING DATES FROM 20020911 TO 20020925

FEPP Fee payment procedure

Free format text: PAYOR NUMBER ASSIGNED (ORIGINAL EVENT CODE: ASPN); ENTITY STATUS OF PATENT OWNER: LARGE ENTITY

AS Assignment

Owner name: BAYER SCHERING PHARMA AKTIENGESELLSCHAFT, GERMANY

Free format text: CHANGE OF NAME;ASSIGNOR:SCHERING AKTIENGESELLSCHAFT;REEL/FRAME:020156/0001

Effective date: 20061229

CC Certificate of correction
FEPP Fee payment procedure

Free format text: PAYER NUMBER DE-ASSIGNED (ORIGINAL EVENT CODE: RMPN); ENTITY STATUS OF PATENT OWNER: LARGE ENTITY

Free format text: PAYOR NUMBER ASSIGNED (ORIGINAL EVENT CODE: ASPN); ENTITY STATUS OF PATENT OWNER: LARGE ENTITY

FPAY Fee payment

Year of fee payment: 4

REMI Maintenance fee reminder mailed
LAPS Lapse for failure to pay maintenance fees
STCH Information on status: patent discontinuation

Free format text: PATENT EXPIRED DUE TO NONPAYMENT OF MAINTENANCE FEES UNDER 37 CFR 1.362

FP Lapsed due to failure to pay maintenance fee

Effective date: 20150626